Pena-Shokeir Syndrome Type 2

Pena-Shokeir syndrome type 2 is a very rare genetic condition in which a baby has very little movement before birth, many stiff joints, webbing of skin across the joints (pterygia), and serious problems with lung development and other organs. [1] Doctors often group type 2 with a very severe form of multiple pterygium syndrome, and most affected babies die before or shortly after birth because the lungs are too small to work properly. [1][2]

Pena-Shokeir syndrome type 2 is a very rare, serious genetic disease. It is also called cerebro-oculo-facio-skeletal (COFS) syndrome. In this condition, a baby is born with many problems in the brain, eyes, face, bones, and joints. The disease gets worse over time. It is usually caused by changes (mutations) in genes that repair damaged DNA in the body’s cells. Because the brain and other organs cannot grow and work normally, children have very slow development, severe disability, and a short life span.

The syndrome is inherited in an autosomal recessive way. This means both parents usually carry one changed copy of a gene, but they are healthy themselves. When a baby receives the changed gene from both parents, the baby develops Pena-Shokeir syndrome type 2. It affects boys and girls equally and has been reported in many parts of the world.

In Pena-Shokeir syndrome type 2, the damaged genes are part of the “nucleotide excision repair” (NER) system. This system normally finds and fixes certain kinds of damage in DNA, such as damage caused by sunlight (UV) or chemicals. When this repair system does not work, DNA damage builds up. Cells in the brain, eyes, and other tissues are especially sensitive, so they slowly stop working and may die. This leads to brain shrinkage (atrophy), joint contractures, and many severe problems from early life.

Pena-Shokeir syndrome type 2 is usually inherited in an autosomal recessive way, meaning both parents silently carry one changed copy of a gene, and the baby receives both changed copies. [2] Different genes involved in nerve–muscle junctions and early muscle development have been linked to this “fetal akinesia sequence,” explaining why reduced movement in the womb leads to fixed joints, facial changes, and lung under-development. [1][2][3]

Because the condition is so severe, many pregnancies are managed with careful monitoring and detailed counselling, and parents are given options about the birth plan, resuscitation, and palliative care. [1] Management is always guided by specialists in fetal medicine, neonatology, genetics, and palliative care; families should never try to manage this condition without expert medical support. [2][4]

Other names

Pena-Shokeir syndrome type 2 has several other names. Doctors may use any of these terms for the same condition:

1. Cerebro-oculo-facio-skeletal syndrome (COFS syndrome) – “cerebro” means brain, “oculo” means eyes, “facio” means face, and “skeletal” means bones and joints.

2. Cerebro-oculo-facial-skeletal syndrome – another spelling for the same group of problems affecting brain, eyes, face, and skeleton.

3. Pena-Shokeir syndrome type II – full medical name, often used in reports and textbooks.

4. COFS type 1, type 2, type 3, type 4 – some experts divide COFS by which DNA-repair gene is affected (for example ERCC6/CSB, ERCC2/XPD, ERCC5/XPG, ERCC1). All of these give a very similar clinical picture of brain, eye, and skeletal damage before and after birth.

Types 

Doctors sometimes talk about “types” of COFS or Pena-Shokeir type 2 based on the main gene involved:

• COFS type 1 (ERCC6/CSB gene) – changes in this DNA repair gene are a common cause of COFS.

• COFS type 2 (ERCC2/XPD gene) – another NER gene; mutations here can also cause a COFS-like picture.

• COFS type 3 (ERCC5/XPG gene) – changes in this gene affect cutting and fixing damaged DNA strands.

• COFS type 4 (ERCC1 gene) – mutations here also disturb DNA repair and can produce a similar syndrome.

Even though names and types differ, the main clinical picture is very similar: progressive brain damage, severe disability, eye problems, contractures, and poor growth.

---

Causes

1. Autosomal recessive inheritance
   The main cause is autosomal recessive inheritance. Both parents usually carry one changed copy of a COFS gene. They are healthy, but when a child receives the changed gene from both parents, the child develops Pena-Shokeir syndrome type 2.

2. Mutation in the ERCC6 (CSB) gene
   One important cause is a mutation in the ERCC6 gene, also called CSB. This gene is part of the DNA repair system. When it does not work, cells cannot repair certain DNA damage, especially in brain and eye tissues, leading to the COFS picture.

3. Mutation in the ERCC2 (XPD) gene
   Some families with Pena-Shokeir type 2 have changes in the ERCC2 gene. This gene helps open the DNA strand so damage can be removed. When it is faulty, DNA cannot be properly fixed, and nerve cells slowly degenerate.

4. Mutation in the ERCC5 (XPG) gene
   Mutations in ERCC5, which cuts damaged pieces of DNA during repair, can also cause a COFS-like syndrome. This again leads to poor repair of DNA in many tissues, especially the brain and eyes.

5. Mutation in the ERCC1 gene
   ERCC1 works with other proteins to remove damaged DNA segments. If this gene is mutated, the repair process is incomplete. The result is similar: progressive damage in the nervous system and other organs in the fetus and child.

6. Defective nucleotide excision repair (NER) pathway
   All these genes are part of the nucleotide excision repair pathway, which normally finds and removes “bulky” DNA damage. When the pathway is defective, cells cannot handle everyday DNA damage and slowly fail. This is a core cause of the disease.

7. Build-up of DNA damage in brain cells
   In Pena-Shokeir type 2, DNA damage is not repaired in brain cells. Over time, this leads to brain shrinkage (atrophy), poor brain growth, and loss of brain function, which explains the severe developmental delay and intellectual disability.

8. Build-up of DNA damage in eye tissues
   The same repair problem affects the eyes. Lens cells and other eye cells cannot fix DNA damage, so cataracts, microcornea (small cornea), and other eye malformations develop before birth.

9. Abnormal skeletal and joint development
   Because growing bone, cartilage, and muscle cells cannot repair their DNA properly, the skeleton and joints do not form normally. This leads to joint contractures, tight muscles, and deformities of the limbs and spine.

10. Abnormal facial development
    DNA repair failure in facial tissues and bones causes typical facial differences, such as small jaw, small head, and deep-set or small eyes. These features help doctors recognize the syndrome.

11. Progressive neurodegeneration
    The disease is not only present at birth but also progressive. Nerve cells continue to be damaged and lost because the repair system does not work. This progressive neurodegeneration is a key reason for worsening stiffness, contractures, and developmental problems.

12. Carrier parents (both with one faulty gene)
    A frequent cause in families is that each parent is a healthy carrier. When they have more than one child, more than one child may be affected because the same recessive gene change is passed on again.

13. Consanguinity (parents related by blood)
    In some reported families, parents are related (for example, cousins). In such families, they are more likely to carry the same rare recessive gene. This increases the chance of having a child with Pena-Shokeir type 2.

14. Compound heterozygous mutations
    Some children may inherit two different mutations in the same gene (one from each parent). Even though the mutations are different, together they stop the gene from working and cause the disease. This pattern is called compound heterozygosity.

15. Genetic heterogeneity (different genes, similar picture)
    The same clinical picture can come from mutations in several different NER genes. This is called genetic heterogeneity. It explains why different families may have different gene changes but a similar COFS/Pena-Shokeir type 2 phenotype.

16. New (de novo) gene mutations
    In some cases, the mutation seems to appear for the first time in the affected child (a new or de novo mutation). This can happen during the formation of egg or sperm cells and can still cause an autosomal recessive pattern if both gene copies are affected.

17. Increased cell sensitivity to UV and chemical damage
    Cells with NER gene defects are unusually sensitive to ultraviolet light and some chemicals at the DNA level. Even normal low-level exposure can cause more DNA damage than usual, adding to the burden on already weak repair systems.

18. Prenatal onset (damage starts before birth)
    The genetic problem is present from conception, so brain, eye, and skeletal damage starts early in pregnancy. This prenatal onset explains why many signs (such as contractures and cataracts) are already seen on ultrasound or at birth.

19. Global effect on many organs
    Because DNA repair genes act in every cell, the defect affects many organs at once, not just the brain. This “whole-body” effect is another cause of the complex mix of problems seen in Pena-Shokeir type 2.

20. Underlying rare-disease genetics
    Pena-Shokeir type 2 is part of a group of very rare genetic DNA-repair disorders. The rarity itself is a consequence of very uncommon gene changes that are usually only seen when both parents carry the same rare mutation.

---

Symptoms

1. Severe developmental delay and intellectual disability
   Children with Pena-Shokeir type 2 have very slow development. They often do not reach normal milestones such as sitting, standing, or talking. Thinking and learning abilities are severely limited because of early and ongoing brain damage.

2. Microcephaly (small head size)
   The head is often smaller than normal because the brain does not grow properly. Doctors measure the head around and compare it to normal charts. In this syndrome, the head size usually falls well below the expected range for age.

3. Brain atrophy (loss of brain tissue)
   Brain scans show that the brain is smaller and may have large fluid spaces because brain tissue has not formed or has been lost. This atrophy explains many of the neurological signs, such as poor movement and seizures.

4. Eye problems: cataracts and microcornea
   A key symptom is eye involvement. Children may be born with cloudy lenses (cataracts), very small corneas, or other eye malformations. These changes can make vision very poor or absent. Eye problems are part of the “oculo” part of the COFS name.

5. Facial differences (dysmorphic features)
   Many children have a typical facial appearance, such as small jaw (micrognathia), high forehead, small eyes, or deep-set eyes. These facial features help doctors think about this diagnosis when they see a newborn.

6. Joint contractures (stiff joints) and arthrogryposis
   The joints of the arms, legs, hands, and feet are often stiff and fixed in bent or straight positions. This is called arthrogryposis. It results from poor fetal movement and abnormal muscle and joint development before birth.

7. Progressive tightening of muscles and tendons
   Over time, muscles and tendons can become tighter. This makes moving the joints even harder and can cause pain or discomfort. Physiotherapists often see both low tone in some muscles and stiffness in others.

8. Spinal deformities (such as scoliosis)
   The spine may curve abnormally because of weak muscles and abnormal bone growth. This curvature, called scoliosis, can worsen with time and may affect sitting balance and breathing.

9. Poor growth and short stature
   Children usually grow more slowly than their peers. Their height, weight, and head size may all be below normal. This poor growth reflects both the underlying genetic problem and feeding and health difficulties.

10. Feeding difficulties and failure to thrive
    Many babies have trouble sucking, swallowing, and coordinating breathing while feeding. They may tire easily and gain weight slowly. Some children need feeding tubes to get enough nutrition safely.

11. Breathing problems and frequent infections
    Because of weak muscles, chest deformities, and neurological problems, breathing can be shallow or weak. Children may have frequent chest infections and may need oxygen or ventilator support, especially during illness.

12. Seizures or abnormal movements
    Some children have seizures because of the severe brain abnormalities. These may show as staring spells, body stiffening, or rhythmic jerking. Seizures need careful medical treatment and monitoring.

13. Hearing loss
    Hearing can also be affected. Children may not respond well to sounds or voices. Hearing tests often show sensorineural hearing loss, meaning the inner ear or nerve pathway is damaged.

14. Mixed muscle tone (floppy then stiff)
    At first, babies may seem very floppy (hypotonic) because muscles and nerves are weak. Later, many develop stiffness (spasticity) as the nervous system continues to be damaged. This mix of low and high tone is common in severe brain disorders.

15. Life-limiting course and early death
    Sadly, Pena-Shokeir syndrome type 2 is usually life-limiting. Many children die in early childhood because of severe infections, breathing problems, or complications of their neurological condition. Some with milder forms may live longer but still need total care.

---

Diagnostic tests

Physical exam tests

1. General newborn and child examination
   Doctors start with a full physical exam. They check head size, body length, weight, joint positions, facial features, and muscle tone. In Pena-Shokeir type 2, they often see microcephaly, contractures, facial differences, and poor muscle control, which raise suspicion of a syndromic condition.

2. Detailed neurological examination
   The neurologist looks at reflexes, muscle tone, strength, and movement. In this syndrome, reflexes may be abnormal, tone may be low or later high, and voluntary movement is limited. These findings support the idea of a severe brain and nerve disorder.

3. Eye and face examination with light
   The doctor examines the eyes with a light to look for cataracts, small corneas, or other abnormalities, and studies the facial shape. Finding both eye and facial abnormalities along with joint contractures points toward COFS/Pena-Shokeir type 2 rather than a simple orthopedic problem.

4. Chest and spine examination
   The chest and spine are checked for deformities such as scoliosis or narrow chest. These problems can affect breathing and are common in conditions with long-standing contractures and muscle weakness.

Manual tests

5. Joint range-of-motion testing
   The doctor gently moves each joint to see how far it can bend or straighten. In Pena-Shokeir type 2, many joints are fixed and do not move normally. This helps document the severity of arthrogryposis and guides physiotherapy planning.

6. Manual muscle strength assessment
   Where possible, clinicians test how strongly the child can push or pull against resistance. Even in young children, they can compare movement on both sides of the body. Weakness and lack of movement support the idea of a global neuromuscular problem.

7. Developmental assessment (simple bedside tests)
   Using simple tasks (like tracking with the eyes, reaching, rolling), therapists assess development. Children with Pena-Shokeir type 2 usually show very delayed or absent skills in all areas, confirming severe neurodevelopmental impairment.

8. Simple vision and hearing response tests
   Clinicians may clap, speak, or shine lights to see whether the child reacts. Weak or absent responses suggest visual or hearing loss and tell the team that formal tests are needed later.

Lab and pathological tests

9. Basic blood tests and metabolic screen
   Blood tests (such as full blood count, liver and kidney tests, and metabolic screens) are done to rule out other treatable conditions that can cause developmental delay or contractures. Normal or nonspecific results support the idea of a primary genetic syndrome.

10. Targeted genetic testing for NER genes
    If doctors suspect COFS/Pena-Shokeir type 2, they may order sequencing of genes such as ERCC6, ERCC2, ERCC5, and ERCC1. Finding two harmful mutations confirms the diagnosis and helps with family counseling about future pregnancies.

11. Gene panel or exome sequencing
    Sometimes a broader gene panel or whole-exome sequencing is used when the exact gene is unknown. These tests look at many genes at once and can still find NER gene mutations or other rare gene problems that mimic COFS.

12. Prenatal genetic testing (CVS or amniocentesis)
    If a family already has one affected child and the gene change is known, doctors can test a future pregnancy using chorionic villus sampling or amniocentesis. Detecting the mutation early helps families make informed decisions.

13. Functional DNA repair assays in fibroblasts
    In research or specialized centers, doctors can take a small skin sample, grow fibroblast cells, and test how well these cells repair DNA damage. Poor repair in a NER pattern supports a diagnosis of a DNA-repair disorder like COFS.

14. Pathology studies (for example, after fetal loss)
    When pregnancy ends early, a pathologist may examine fetal tissues and placenta. They look for joint contractures, facial anomalies, eye changes, and brain underdevelopment. These pathological findings, together with clinical and genetic information, help confirm Pena-Shokeir type 2.

Electrodiagnostic tests

15. Electroencephalogram (EEG)
    EEG records the brain’s electrical activity. In this syndrome, it may show abnormal patterns or epileptic discharges if the child has seizures. EEG helps guide seizure treatment and gives more information about brain function.

16. Nerve conduction studies (NCS)
    NCS measure how fast electrical signals travel along nerves. In some children with severe contractures and weakness, these tests help show whether peripheral nerves are also affected, beyond the primary brain problem.

17. Electromyography (EMG)
    EMG records muscle electrical activity. It can help separate muscle disease from nerve or brain disease. In Pena-Shokeir type 2, EMG findings may show chronic changes related to poor nerve input and immobility.

Imaging tests

18. Brain MRI (magnetic resonance imaging)
    MRI of the brain is a key test. It can show brain atrophy, thin brain structures, and other malformations. These findings explain the severe neurological symptoms and help distinguish COFS from other causes of contractures and delay.

19. Brain CT scan (for calcifications)
    A CT scan uses X-rays to capture detailed images of the brain. In some children with COFS, CT may show calcium deposits inside the brain and further signs of brain damage, supporting the diagnosis.

20. Prenatal ultrasound and fetal MRI
    During pregnancy, ultrasound can show reduced fetal movement, joint contractures, small head, and other abnormalities. In some cases, fetal MRI gives more detail about the brain. These prenatal imaging tests can suggest Pena-Shokeir spectrum and help plan care and counseling.

---

Non-pharmacological (non-drug) treatments and supports

1. Detailed prenatal counselling
When Pena-Shokeir syndrome type 2 is suspected on ultrasound, parents need long, clear meetings with maternal–fetal medicine and genetics specialists to understand the diagnosis, risks, and options. [1] This counselling explains the likely outcome (often lethal), discusses possible comfort-focused care, and helps families make informed, culturally sensitive choices about continuing pregnancy and birth plans. [1][2]

2. High-quality prenatal imaging and monitoring
Serial detailed ultrasounds and sometimes fetal MRI are used to assess joint contractures, lung size, fluid around the baby, and growth. [2] These images cannot cure the condition, but they guide planning for the time and place of birth, and help identify any milder or overlapping forms that might have a slightly better outlook. [1][3] [1]

3. Birth planning in a tertiary center
Delivery is usually planned in a hospital with a neonatal intensive care unit and experienced specialists. [1] This allows immediate assessment of breathing, heart function, and comfort, and supports either active resuscitation in uncertain cases or palliative comfort care when the condition is clearly lethal. [1][4] [2]

4. Neonatal resuscitation decisions
At birth, the team and parents decide together how intensive resuscitation should be. [1] In many clearly lethal cases, only brief assessment and gentle measures are used to avoid painful procedures, but in uncertain or milder situations, standard neonatal resuscitation may be tried while the prognosis becomes clearer. [1][4] [3]

5. Gentle respiratory support
Some babies receive oxygen by mask or nasal prongs to relieve shortness of breath. [3] In selected cases, short-term ventilator support may be used to see whether breathing can be maintained, but long-term ventilation is usually not recommended because lung hypoplasia (tiny lungs) typically cannot be corrected. [1][4] [4]

6. Positioning and handling for comfort
Because joints are stiff and limbs may be fixed, special positioning with soft rolls and cushions helps reduce pain, skin pressure, and breathing difficulty. [3] Nurses and therapists teach parents how to hold and move the baby gently, protecting fragile joints and allowing skin-to-skin contact when possible. [3][4] [5]

7. Specialist physiotherapy (where survival allows)
In rare milder or overlapping forms that survive longer, physiotherapists design gentle range-of-motion exercises to keep joints as flexible as possible. [2] Movement helps reduce contracture pain, improves posture and positioning, and may support breathing mechanics, but the underlying genetic problem cannot be reversed. [2][3] [6]

8. Occupational therapy and adaptive equipment
Occupational therapists support feeding, positioning, and basic care routines using customized cushions, wedges, and adaptive seating. [3] In longer-term survivors, they also advise on splints and devices that make hygiene and handling easier for caregivers, always balancing benefit with comfort. [3][4] [7]

9. Nutritional support and safe feeding
Many babies have weak swallowing and a high risk of aspiration (milk going into the lungs). [2] Speech and feeding therapists may suggest special nipples, thickened feeds, or, in selected longer-surviving cases, tube feeding to maintain comfort and nutrition while trying to avoid repeated choking episodes. [2][4] [8]

10. Pain and comfort assessment (non-drug)
Even non-verbal babies show signs of discomfort through facial expression, heart rate, and breathing. [3] Nurses use validated neonatal pain scales and non-drug methods such as swaddling, gentle rocking, skin-to-skin contact, and dim lighting to lower stress and discomfort whenever possible. [3][4] [9]

11. Palliative care consultation
Early involvement of pediatric palliative care services helps families understand the likely course, define what “comfort” means to them, and plan for symptom relief and memory-making. [1] This team supports spiritual, emotional, and social needs, not just physical symptoms, and continues to help parents after a baby’s death. [1][4][10]

12. Family psychological support and grief care
Psychologists, social workers, and chaplains provide counselling before and after birth, helping parents deal with shock, guilt, sadness, and difficult decisions. [4] Ongoing grief support and sibling support groups reduce long-term mental health problems after such a devastating diagnosis. [4][10] [11]

13. Genetic counselling for parents and relatives
Because Pena-Shokeir syndrome type 2 is usually autosomal recessive, parents have a one-in-four recurrence risk in each future pregnancy. [2] Genetic counselling explains this risk, discusses carrier testing for family members, and reviews options such as early ultrasound, targeted genetic testing, or preimplantation genetic testing in future pregnancies. [2][12] [12]

14. Coordination of multidisciplinary care
The condition touches many systems, so care is best coordinated in case conferences that include neonatology, genetics, neurology, orthopedics, anesthesia, palliative care, nursing, and social work. [1] Good coordination avoids repeated invasive tests, reduces conflicting messages to parents, and makes the care plan consistent and clear. [1][3] [13]

15. Infection prevention and basic nursing care
Babies with poor movement and respiratory weakness have a high risk of pneumonia and other infections. [3] Strict hand hygiene, careful suctioning, regular mouth care, turning schedules, and skin protection are vital to maintain comfort and reduce avoidable suffering, even when care is purely palliative. [3][4] [14]

16. Ethical decision-making support
Ethics consultations can help families and clinicians decide about starting or stopping ventilation, tube feeding, or surgery when the prognosis is extremely poor. [1] These sessions explore values, culture, religion, and the child’s best interests, aiming to avoid both unnecessary suffering and unwanted prolongation of dying. [1][4][15]

17. Documentation of advanced care plans
Clear written care plans record the decisions that have been made about resuscitation, transfer to intensive care, and preferred place of care or death. [4] This documentation helps emergency teams and new staff respect the family’s wishes and reduces repeated, painful discussions in crises. [4][10] [16]

18. Creating memories with the family
Many palliative care teams help families create handprints, photographs, and memory boxes, and encourage skin-to-skin contact when possible. [4] These non-medical acts can greatly help parents in grief and are an important part of holistic care for lethal congenital conditions like Pena-Shokeir syndrome type 2. [4][10] [17]

19. Community and home-based support (where survival allows)
If a baby survives longer and is discharged, community nursing, home oxygen, and home palliative care teams can support the family in their own environment. [1] This reduces hospital time, allows more normal family life, and helps parents feel more in control of daily care. [1][4][18]

20. Support groups and peer connections
Although extremely rare, some families connect through rare-disease networks, online forums, or bereavement groups. [4] Hearing from other parents who faced similar decisions can reduce isolation, offer practical tips, and validate difficult feelings about hope, guilt, and loss. [4][10][19]

---

Drug treatments (supportive, not curative)

Important: There is no medicine that cures or reverses Pena-Shokeir syndrome type 2. Medicines are used only to ease symptoms or treat complications and are always prescribed and dosed by specialists. [1][4]

1. Baclofen for severe spasticity (carefully selected survivors)
Baclofen is a muscle relaxant that acts as a GABA-B receptor agonist in the spinal cord to reduce spasticity. [1] FDA-approved baclofen products (oral and intrathecal) are labeled for spasticity due to conditions like multiple sclerosis or spinal cord disease, not for Pena-Shokeir itself, but may be considered off-label in rare longer-term survivors with painful contractures. [1][5] Dose is carefully weight-based and slowly increased to avoid drowsiness, breathing depression, and withdrawal if stopped suddenly. [5][6]

2. Gabapentin for neuropathic pain or seizures
Gabapentin binds to voltage-gated calcium channel subunits and is approved by FDA for seizures and neuropathic pain in older patients. [2] In theoretical or overlapping milder neuromuscular cases, specialists might use it off-label to help neuropathic pain or refractory seizures, but safety and dosing in fragile neonates require extreme caution and specialist oversight. [2][7] Typical dosing is titrated slowly, as labels warn about sedation, dizziness, and mood changes. [7][8]

3. Standard antiepileptic drugs
Some babies with fetal akinesia syndromes may develop seizures, and standard antiepileptic medicines such as phenobarbital or levetiracetam can be used according to neonatal protocols. [3] These drugs aim to stabilize brain electrical activity, reduce seizure frequency, and prevent additional brain injury, but they do not change the underlying syndrome. [3][4] Dosing is strictly weight-based, with monitoring for sedation, blood count changes, and liver effects. [3][4] [3]

4. Opioid analgesics for severe pain or air hunger in palliative care
Low-dose opioids such as morphine may be used to relieve severe pain or the feeling of air hunger in babies with end-stage lung failure. [4] They act on opioid receptors to reduce pain perception and decrease the sensation of breathlessness, allowing more peaceful breathing. [4][10] Dosing is very small and carefully monitored to balance comfort with side effects like drowsiness and slowed breathing. [4] [4]

5. Acetaminophen for mild-to-moderate pain and fever
Acetaminophen (paracetamol) is widely used in neonates to relieve mild pain or fever, including discomfort from procedures or joint stiffness. [3] It acts centrally to reduce pain and fever without the stomach and kidney side effects seen with many NSAIDs, but doses must be carefully calculated to avoid liver toxicity. [3][4] In this syndrome it is part of basic comfort care, not a disease-modifying treatment. [3] [5]

6. Broad-spectrum antibiotics for suspected infection
Babies with severe lung and movement problems are at high risk of pneumonia and sepsis. [3] When infection is suspected, doctors often start intravenous broad-spectrum antibiotics such as ampicillin plus gentamicin, following neonatal sepsis guidelines, to quickly cover common bacteria while cultures are checked. [3][4] Doses are adjusted for weight and kidney function to limit toxicity. [3] [6]

7. Surfactant therapy for severe respiratory distress (selected cases)
If a preterm or structurally borderline baby with Pena-Shokeir type 2 shows respiratory distress syndrome, clinicians may give surfactant into the lungs via a breathing tube. [1] Surfactant reduces surface tension in tiny air sacs, helping them stay open and improving oxygen exchange; however, in true lung hypoplasia the benefit may be limited. [1][3] Decisions depend on overall prognosis and family wishes. [1] [7]

8. Diuretics in selected heart or lung fluid overload
If there is evidence of heart failure or significant lung fluid, low-dose diuretics such as furosemide may be used to remove extra fluid and improve breathing comfort. [3] These medicines act on the kidneys to increase urine output, reducing swelling and congestion, but they can cause electrolyte loss and require blood tests and close monitoring. [3][4] [8]

9. Anti-reflux therapy for severe gastroesophageal reflux
Babies with weak muscle tone and abnormal posture often have reflux, which can worsen breathing and cause pain. [2] Doctors may prescribe proton pump inhibitors or H2 blockers to reduce stomach acid, along with thickened feeds and positioning strategies, to decrease heartburn and reduce aspiration risk. [2][3] Side effects and long-term use are weighed carefully in palliative situations. [2] [9]

10. Sedatives for distress in end-of-life care (very carefully used)
In some end-of-life situations, small doses of sedative medicines, sometimes combined with opioids, may be used to ease severe agitation or distress that cannot be controlled otherwise. [4] These drugs act on the brain to reduce awareness of discomfort, and their use is carefully discussed with the family as part of palliative sedation, always aiming to relieve suffering rather than shorten life. [4][10] [10]

---

Dietary molecular supplements (supportive, only under specialist advice)

In classic Pena-Shokeir syndrome type 2, many babies cannot feed normally and live only a short time, so supplements are often not relevant. The ideas below refer mainly to theoretical or milder overlapping conditions and must only be used under specialist supervision. [1][2]

1. High-calorie pediatric formulas can be used via bottle or feeding tube to provide more energy in small volumes, supporting growth and healing in longer-term survivors. [1][3] They include balanced protein, fats, and carbohydrates and help prevent malnutrition when feeding is difficult. [1] [1]

2. Omega-3 fatty acids from medical-grade fish-oil preparations may support brain and nerve health and have mild anti-inflammatory effects, but evidence in this syndrome is indirect and limited. [2] Doses are based on body weight, and purity and safety (no heavy metals) are essential. [2][3] [2]

3. Vitamin D helps with bone mineralization and immune function and is often supplemented in babies with little sunlight exposure or poor intake. [3] Dosing is usually a small daily drop, carefully adjusted to avoid toxicity and monitored by blood tests. [3][4] [3]

4. Calcium may be given alongside vitamin D when there is poor bone mineralization or risk of osteoporosis due to immobility. [3] Excess calcium can cause kidney stones or abnormal rhythms, so dosing must follow lab values. [3][4] [4]

5. Multivitamin drops provide small amounts of many vitamins for babies with limited varied intake. [2] They support general metabolism but are not disease-specific; fat-soluble vitamins (A, D, E, K) must not be overdosed. [2][3] [5]

6. Probiotics may help gut health and reduce some infections in high-risk infants, but evidence is mixed and strain-specific. [3] In very premature or immunocompromised babies, they are used cautiously because of rare risks of bloodstream infection. [3][4] [6]

7. L-carnitine supports fatty acid transport in mitochondria and is sometimes used in neuromuscular conditions with proven carnitine deficiency. [2] It has no proven benefit specifically in Pena-Shokeir type 2 and should only be used if deficiency is documented. [2][3] [7]

8. Coenzyme Q10 is an antioxidant involved in mitochondrial energy production and is used experimentally in some neuromuscular diseases. [3] There is no clear evidence that it helps fetal akinesia syndromes, so any use is off-label and research-oriented. [3][4] [8]

9. Zinc supplementation may be considered if blood levels are low, because zinc is important for immunity and wound healing. [3] Too much zinc can interfere with copper and other minerals, so laboratory monitoring is needed. [3][4] [9]

10. Iron supplementation is used only if iron-deficiency anemia is present. [3] Iron supports oxygen transport and energy but can worsen infections if used unnecessarily; therefore, it is always lab-guided. [3][4] [10]

---

Immunity-booster / regenerative / stem-cell approaches

1. No approved stem-cell cure
   There is no approved stem-cell or regenerative drug that can cure Pena-Shokeir syndrome type 2 or reverse its severe lung under-development and joint contractures. [1] Any claims of “stem-cell cures” outside rigorously monitored research studies should be viewed with extreme caution. [1][2] [1]

2. Experimental gene-targeted therapies
   In theory, if a specific disease-causing gene is identified, future gene therapies might be explored, similar to treatments in other neuromuscular diseases. [2] At present, such therapies for fetal akinesia or multiple pterygium syndromes remain experimental and are not part of standard care. [2][3] [2]

3. Immune-modulating drugs (IVIG, biologics) – not standard here
   Some immune-modulating treatments are used in acquired neuromuscular diseases, but Pena-Shokeir type 2 is usually a structural genetic disorder, not an autoimmune condition. [1] Therefore, IVIG or biologic agents are not standard and would only be considered in research settings or in unusual overlapping cases. [1][3] [3]

4. Support of natural immunity with good nursing and nutrition
   The most realistic “immunity support” is basic: breastfeeding when possible, infection prevention measures, and adequate calories and micronutrients. [3] These help the baby fight infections but cannot change the underlying syndrome. [3][4] [4]

5. Rehabilitation-driven regeneration in milder overlap cases
   In rare milder or different but related neuromuscular conditions, intensive physiotherapy and occupational therapy may help the nervous system and muscles use remaining capacity more effectively. [2] This functional “regeneration” is limited and does not apply to classic lethal Pena-Shokeir type 2. [2][3] [5]

6. Enrollment in carefully regulated clinical trials
   If, in the future, gene or cell-based trials become available for fetal akinesia syndromes, participation should be through regulated clinical trials with full informed consent and safety monitoring. [1] Families should avoid unregulated “stem-cell clinics” that are expensive, risky, and not evidence-based. [1][4] [6]

---

Surgeries

1. Tracheostomy for longer-term airway support
   In unusual survivors with ongoing but stable respiratory failure, a tracheostomy (a breathing tube placed through the neck into the windpipe) may be considered. [3] It allows long-term ventilation and easier airway care but represents a major lifelong dependence on machines and is rarely appropriate in classic lethal Pena-Shokeir type 2. [3][4] [1]

2. Gastrostomy tube placement
   A gastrostomy (feeding tube placed directly into the stomach) may be used when oral feeding is unsafe due to severe swallowing problems. [2] It reduces aspiration risk, eases medication delivery, and can improve comfort in longer-term survivors or related syndromes, but the risks and goals of care must be carefully discussed. [2][3] [2]

3. Orthopedic tendon-release and contracture-release surgery
   If a child with a related but less severe multiple pterygium or contracture syndrome survives longer, orthopedic surgeons may release tight tendons and soft tissues around joints. [2] These operations aim to improve limb position and hygiene, but results are limited when muscles and nerves are intrinsically abnormal. [2][3] [3]

4. Scoliosis or spine surgery
   Severe spine curvature due to muscle imbalance and contractures might be surgically corrected in selected children with longer survival and functional goals. [3] Surgery tries to improve posture and sitting balance, but it carries significant risks, especially in children with lung weakness. [3][4] [4]

5. Minor procedures for comfort (e.g., skin contracture release)
   Small procedures, such as releasing skin webbing that causes pressure sores or hygiene problems, may be done for comfort rather than function. [3] These are individualized and always weighed against anesthesia and recovery risks in a medically fragile child. [3][4] [5]

---

Prevention and risk-reduction strategies

Because Pena-Shokeir syndrome type 2 is usually genetic, it cannot be fully “prevented,” but some steps can reduce recurrence risk or allow earlier detection. [2] [1]

1. Pre-pregnancy genetic counselling for at-risk couples [1]

2. Carrier testing of parents and, when appropriate, siblings or extended family [2]

3. Considering preimplantation genetic testing with IVF when a specific mutation is known [3]

4. Early targeted ultrasound in future pregnancies for couples with a previous affected child [2]

5. Timely referral to high-risk obstetric and fetal medicine centers when fetal movement appears reduced [1]

6. Avoidance of consanguineous marriage when a specific recessive risk is known in the family [2]

7. Optimizing maternal health (e.g., nutrition, chronic disease control) to reduce additional fetal stress [3]

8. Avoiding known teratogens (certain drugs, toxins, infections) during pregnancy as advised by obstetricians [3]

9. Participation in registries and research to better understand genetic causes and future prevention [1]

10. Providing clear written information to families so they can share accurate risk details with relatives [2]

---

When to see doctors

Parents or pregnant people should urgently see doctors if ultrasound shows reduced fetal movement, multiple joint contractures, abnormal facial features, or suspected small lungs, especially with a history of Pena-Shokeir syndrome in the family. [1][2] Any such findings need rapid referral to a maternal–fetal medicine specialist and genetic counsellor. [1][2][3]

Families who have already had an affected child should see a clinical geneticist before planning another pregnancy to discuss carrier testing, recurrence risk, and options such as early targeted ultrasound and genetic testing in future pregnancies. [2] [1]

Any baby born with fixed joints, facial differences, poor movement, and breathing problems needs immediate assessment by a neonatologist in a specialist center, because these signs can indicate Pena-Shokeir syndrome type 2 or other serious neuromuscular syndromes. [1][3]

---

What to eat and what to avoid

Again, most babies with classic Pena-Shokeir syndrome type 2 will not survive long enough for complex dietary plans. [1] These points apply mainly to rare, milder, overlapping conditions and must be guided by pediatric nutritionists. [1][3]

What to prioritize (when oral or tube feeding is possible)

1. Energy-dense feeds – high-calorie formulas or breast milk fortifiers to support growth with small volumes. [1]

2. Adequate protein – to support muscle and tissue repair, using infant-appropriate formulas or, later, soft high-protein foods. [2]

3. Balanced fats, including omega-3s – to help brain and nerve health, within pediatric dosing limits. [3]

4. Micronutrient-rich foods or prescribed supplements – to avoid vitamin and mineral deficiencies. [3]

5. Safe consistencies – thickened or pureed textures to match swallowing ability and reduce choking risk. [2]

What to be careful with or avoid

1. Thin liquids in babies with aspiration risk – may flow too fast and enter the airway. [3]
2. Hard, mixed-texture foods in older children with chewing or swallowing problems. [3]
3. Excessive sugary drinks – raise dental caries and do not add helpful nutrients. [4]
4. Unregulated “miracle” supplements or stem-cell products sold online – often expensive, untested, and sometimes dangerous. [1]
5. Any diet that limits calories or key nutrients in an already fragile child, unless carefully supervised by specialists. [3]

---

FAQs

1. Is Pena-Shokeir syndrome type 2 the same as type 1?
No. Type 1 usually refers to fetal akinesia deformation sequence without pterygia, while type 2 is often used for a very severe form of multiple pterygium syndrome with similar reduced movement but prominent webbing across joints. [1][2] Both forms are usually lethal, with serious lung under-development. [1]

2. What causes the syndrome?
It is usually caused by changes (mutations) in genes involved in nerve–muscle communication and early muscle development, inherited in an autosomal recessive pattern. [2] Reduced fetal movement then leads to fixed joints, facial changes, and small lungs. [2][3]

3. Can anything in pregnancy “cause” it, like food or exercise?
In most cases, parents did nothing wrong: the main cause is genetic. [2] Usual foods, exercise, or minor illnesses in pregnancy do not cause Pena-Shokeir syndrome type 2. Doctors still check for other conditions that can also reduce fetal movement. [2][3]

4. Can my baby survive with this diagnosis?
Sadly, most babies with true Pena-Shokeir syndrome type 2 die before birth or shortly after delivery because their lungs are too small. [1] Occasionally, milder or overlapping cases may survive longer, but this is uncommon and needs careful specialist assessment. [1][4]

5. Is there a cure?
No cure currently exists. [1] Treatment focuses on comfort, gentle breathing support when appropriate, and emotional support for the family, often under palliative care teams. [1][4]

6. Are there specific medicines for Pena-Shokeir syndrome type 2?
There are no medicines that specifically treat or reverse the syndrome. [1] Drugs such as baclofen or gabapentin can sometimes be used off-label to relieve symptoms like spasticity or pain in related conditions, but they do not change the underlying disease. [1][5][7]

7. Could surgery fix the joints or lungs?
Surgery cannot repair lung under-development. [1] Orthopedic surgeries may help joint position in rare longer-surviving or milder overlapping cases, but they do not cure the condition and are not usually possible in classic lethal type 2 cases. [1][3]

8. What is palliative care and why is it recommended?
Palliative care is specialized medical care that focuses on comfort and quality of life for babies with serious, often lethal conditions. [4] It helps manage pain, breathing difficulty, and emotional needs, and supports families with decision-making and grief. [4][10]

9. Will we be able to hold our baby?
In most cases, yes. [4] Even with severe illness, teams try to allow skin-to-skin contact, cuddling, and memory-making while keeping the baby as comfortable as possible. [4][10]

10. Can we have more children, and what is the risk?
If the condition is autosomal recessive, each future pregnancy has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected. [2] Exact risk is confirmed through genetic testing and counselling. [2][12]

11. What tests can be done in a future pregnancy?
Depending on the identified gene change, options include early targeted ultrasound, chorionic villus sampling, amniocentesis, and sometimes preimplantation genetic testing in IVF. [2] A clinical geneticist can explain which options are available locally. [2][3]

12. Is it my fault that this happened?
No. Genetic conditions like Pena-Shokeir syndrome type 2 are not caused by anything parents intentionally did. [2] It is natural to feel guilt, but counselling and support groups can help parents process these feelings. [2][4]

13. Are stem-cell or “regenerative” treatments available abroad?
At present there are no proven, approved stem-cell or regenerative treatments for Pena-Shokeir syndrome type 2. [1] Many advertised “stem-cell cures” are unregulated and may be unsafe or exploitative. [1][4]

14. How can we cope emotionally with this diagnosis?
Talking with palliative care teams, psychologists, chaplains, and families with similar experiences can help. [4] Creating memories with the baby, even if life is very short, often becomes deeply meaningful in the grieving process. [4][10]

15. Where can we find more information?
Reliable information can be found through rare-disease organizations, genetic counseling services, and peer-reviewed medical articles, preferably accessed and explained by your medical team. [1][2] They can help you understand complex terms and avoid misleading sources. [1][2][4]

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: February 02, 2025.